Association of GRP78, HIF-1α and BAG3 Expression with the Severity of Chronic Lymphocytic Leukemia

Author(s): Roghayeh Ijabi, Parisa Roozehdar, Reza Afrisham, Hemen Moradi-Sardareh, Saeed Kaviani, Janat Ijabi*, Amirhossein Sahebkar

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 4 , 2020

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Graphical Abstract:


Abstract:

Introduction: Parallel with the progression of Chronic Lymphocytic Leukemia (CLL), the levels of 78KDa Glucose-Regulated Protein (GRP78) and Hypoxia-Inducible Factor 1 alpha (HIF-1α) are increased as they may activate the induction of anti-apoptotic proteins such as BCL2 Associated Athanogene 3 (BAG3). Previous studies have indicated that there is a positive correlation among GRP78, HIF-1α and BAG3.

Objective: This study aimed to evaluate the effect of metabolic factors involved in invasive CLL on apoptotic factors.

Methods: A case-control study was conducted on 77 patients diagnosed with CLL along with 100 healthy individuals. Cell blood count was performed for all participants. According to Binet's classification, CLL patients were divided into different groups. B cells were isolated from the peripheral blood of CLL patients by binding to anti-CD19 beads. The expression of BAG3, GRP78 and HIF-1α genes was analyzed using the RT-PCR method. To confirm the results of RT-PCR, western blot analysis was carried out.

Results: The results showed that there was a strong association among the expression of BAG3, GRP78 and HIF-1α. The stage of CLL in patients was highly correlated with the expression rate of each gene (p<0.001). Accordingly, the western blot analysis indicated that the concentrations of GRP78 and HIF-1α were significantly higher than the expression of BAG3, considering the stage of CLL.

Conclusion: It was shown that increased expression of GRP78 and HIF-1α could result in the elevation of BAG3, as well as the disease progression. Therefore, the role of these metabolic factors might be more pronounced compared with the anti-apoptotic agents to monitor disease progression in CLL patients.

Keywords: CLL, RT-PCR, western blot, GRP78, HIF-1α, BAG3.

[1]
Chiorazzi, N.; Rai, K.R.; Ferrarini, M. Chronic lymphocytic leukemia. N. Engl. J. Med., 2005, 352(8), 804-815.
[http://dx.doi.org/10.1056/NEJMra041720] [PMID: 15728813]
[2]
Kokhaei, P.; Rezvany, M.R.; Virving, L.; Choudhury, A.; Rabbani, H.; Österborg, A.; Mellstedt, H. Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL. Leukemia, 2003, 17(5), 894-899.
[http://dx.doi.org/10.1038/sj.leu.2402913] [PMID: 12750703]
[3]
Solans, M.; Osca-Gelis, G.; Comas, R.; Roncero, J.M.; Gallardo, D.; Marcos-Gragera, R.; Saez, M. Challenges in assessing the real incidence of chronic lymphocytic leukemia: 16 years of epidemiological data from the province of Girona, Spain. Cancer Causes Control, 2018, 29(3), 379-382.
[http://dx.doi.org/10.1007/s10552-018-1004-5] [PMID: 29383469]
[4]
Brito-Babapulle, V.; Pittman, S.; Melo, J.V.; Pomfret, M.; Catovsky, D. Cytogenetic studies on prolymphocytic leukemia. 1. B-cell prolymphocytic leukemia. Hematol. Pathol., 1987, 1(1), 27-33.
[PMID: 3509770]
[5]
Arima, H.; Ono, Y.; Tabata, S.; Matsushita, A.; Hashimoto, H.; Ishikawa, T.; Takahashi, T. Successful allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for B-cell prolymphocytic leukemia in partial remission. Int. J. Hematol., 2014, 99(4), 519-522.
[http://dx.doi.org/10.1007/s12185-014-1505-2] [PMID: 24470149]
[6]
D’Arena, G.; Di Renzo, N.; Brugiatelli, M.; Vigliotti, M.L.; Keating, M.J. Biological and clinical heterogeneity of B-cell chronic lymphocytic leukemia. Leuk. Lymphoma, 2003, 44(2), 223-228.
[http://dx.doi.org/10.1080/1042819021000035756] [PMID: 12688337]
[7]
Alfarano, A.; Indraccolo, S.; Circosta, P.; Minuzzo, S.; Vallario, A.; Zamarchi, R.; Fregonese, A.; Calderazzo, F.; Faldella, A.; Aragno, M.; Camaschella, C.; Amadori, A.; Caligaris-Cappio, F. An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. Blood, 1999, 93(7), 2327-2335.
[http://dx.doi.org/10.1182/blood.V93.7.2327] [PMID: 10090943]
[8]
Ouchida, R.; Mori, H.; Hase, K.; Takatsu, H.; Kurosaki, T.; Tokuhisa, T.; Ohno, H.; Wang, J-Y. Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. Proc. Natl. Acad. Sci. USA, 2012, 109(40), E2699-E2706.
[http://dx.doi.org/10.1073/pnas.1210706109] [PMID: 22988094]
[9]
Hasserjian, R.P. Chronic lymphocytic leukemia, small lymphocytic lymphoma, and monoclonal B-cell lymphocytosis. Surg. Pathol. Clin., 2010, 3(4), 907-931.
[http://dx.doi.org/10.1016/j.path.2010.09.009] [PMID: 26839294]
[10]
Cairns, R.A.; Harris, I.S.; Mak, T.W. Regulation of cancer cell metabolism. Nat. Rev. Cancer, 2011, 11(2), 85-95.
[http://dx.doi.org/10.1038/nrc2981] [PMID: 21258394]
[11]
Koczula, K.M.; Ludwig, C.; Hayden, R.; Cronin, L.; Pratt, G.; Parry, H.; Tennant, D.; Drayson, M.; Bunce, C.M.; Khanim, F.L.; Günther, U.L. Metabolic plasticity in CLL: adaptation to the hypoxic niche. Leukemia, 2016, 30(1), 65-73.
[http://dx.doi.org/10.1038/leu.2015.187] [PMID: 26202928]
[12]
Polet, F.; Feron, O. Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force. J. Intern. Med., 2013, 273(2), 156-165.
[http://dx.doi.org/10.1111/joim.12016] [PMID: 23216817]
[13]
Murugesan, R.; English, S.; Reijnders, K.; Yamada, K.; Cook, J.A.; Mitchell, J.B.; Subramanian, S.; Krishna, M.C. Fluorine electron double resonance imaging for 19F MRI in low magnetic fields. Magn. Reson. Med., 2002, 48(3), 523-529.
[http://dx.doi.org/10.1002/mrm.10221] [PMID: 12210918]
[14]
Chong, M.N.F.; Challali, L.; Abbar, S.; Etchebest, C. How GLUT1 transporter accompanies glucose along transport: A detailed atomistic view of the mechanism. Biophys. J., 2018, 114(3), 188.
[http://dx.doi.org/10.1016/j.bpj.2017.11.1053]
[15]
Deng, D.; Xu, C.; Sun, P.; Wu, J.; Yan, C.; Hu, M.; Yan, N. Crystal structure of the human glucose transporter GLUT1. Nature, 2014, 510(7503), 121-125.
[http://dx.doi.org/10.1038/nature13306] [PMID: 24847886]
[16]
Liu, Y.; Cao, Y.; Zhang, W.; Bergmeier, S.; Qian, Y.; Akbar, H.; Colvin, R.; Ding, J.; Tong, L.; Wu, S.; Hines, J.; Chen, X. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol. Cancer Ther., 2012, 11(8), 1672-1682.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0131] [PMID: 22689530]
[17]
Lee, K.; Kang, J.E.; Park, S-K.; Jin, Y.; Chung, K-S.; Kim, H-M.; Lee, K.; Kang, M.R.; Lee, M.K.; Song, K.B.; Yang, E.G.; Lee, J.J.; Won, M. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1α via upregulation of VHL in a colon cancer cell line. Biochem. Pharmacol., 2010, 80(7), 982-989.
[http://dx.doi.org/10.1016/j.bcp.2010.06.018] [PMID: 20599784]
[18]
Lee, J.H.; Elly, C.; Park, Y.; Liu, Y-C. E3 ubiquitin ligase VHL regulates hypoxia-inducible factor-1α to maintain regulatory T cell stability and suppressive capacity. Immunity, 2015, 42(6), 1062-1074.
[http://dx.doi.org/10.1016/j.immuni.2015.05.016] [PMID: 26084024]
[19]
Gossage, L.; Eisen, T.; Maher, E.R. VHL, the story of a tumour suppressor gene. Nat. Rev. Cancer, 2015, 15(1), 55-64.
[http://dx.doi.org/10.1038/nrc3844] [PMID: 25533676]
[20]
Kamura, T.; Sato, S.; Iwai, K.; Czyzyk-Krzeska, M.; Conaway, R.C.; Conaway, J.W. Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl. Acad. Sci. USA, 2000, 97(19), 10430-10435.
[http://dx.doi.org/10.1073/pnas.190332597] [PMID: 10973499]
[21]
Basu, R.K.; Hubchak, S.; Hayashida, T.; Runyan, C.E.; Schumacker, P.T.; Schnaper, H.W. Interdependence of HIF-1α and TGF-β/Smad3 signaling in normoxic and hypoxic renal epithelial cell collagen expression. Am. J. Physiol. Renal Physiol., 2011, 300(4), F898-F905.
[http://dx.doi.org/10.1152/ajprenal.00335.2010] [PMID: 21209004]
[22]
Darby, I.A.; Hewitson, T.D. Hypoxia in tissue repair and fibrosis. Cell Tissue Res., 2016, 365(3), 553-562.
[http://dx.doi.org/10.1007/s00441-016-2461-3] [PMID: 27423661]
[23]
Lee, A.S. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res., 2007, 67(8), 3496-3499.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0325] [PMID: 17440054]
[24]
Yadav, R.K.; Chae, S-W.; Kim, H-R.; Chae, H.J. Endoplasmic reticulum stress and cancer. J. Cancer Prev., 2014, 19(2), 75-88.
[http://dx.doi.org/10.15430/JCP.2014.19.2.75] [PMID: 25337575]
[25]
Evans, C.G.; Chang, L.; Gestwicki, J.E. Heat shock protein 70 (hsp70) as an emerging drug target. J. Med. Chem., 2010, 53(12), 4585-4602.
[http://dx.doi.org/10.1021/jm100054f] [PMID: 20334364]
[26]
Asling, J.; Morrison, J.; Mutsaers, A.J. Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy. Cell Stress Chaperones, 2016, 21(6), 1065-1076.
[http://dx.doi.org/10.1007/s12192-016-0730-4] [PMID: 27631331]
[27]
Lee, A.S. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods, 2005, 35(4), 373-381.
[http://dx.doi.org/10.1016/j.ymeth.2004.10.010] [PMID: 15804610]
[28]
Imai, H.; Kaira, K.; Yazawa, T.; Shimizu, A.; Nagashima, T.; Ohtaki, Y.; Obayashi, K.; Asao, T.; Oyama, T.; Shimizu, K. Endoplasmic reticulum stress sensor GRP78/BiP expression in lung adenocarcinoma: Correlations and prognostic significance. Int. J. Clin. Exp. Pathol., 2017, 10(3), 3315-3326.
[29]
Li, J.; Ni, M.; Lee, B.; Barron, E.; Hinton, D.R.; Lee, A.S. The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. Cell Death Differ., 2008, 15(9), 1460-1471.
[http://dx.doi.org/10.1038/cdd.2008.81] [PMID: 18551133]
[30]
Jagannathan, S.; Abdel-Malek, M.A.; Malek, E.; Vad, N.; Latif, T.; Anderson, K.C.; Driscoll, J.J. Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib. Leukemia, 2015, 29(11), 2184-2191.
[http://dx.doi.org/10.1038/leu.2015.157] [PMID: 26108695]
[31]
Lee, A.S. Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential. Nat. Rev. Cancer, 2014, 14(4), 263-276.
[http://dx.doi.org/10.1038/nrc3701] [PMID: 24658275]
[32]
Macheda, M.L.; Rogers, S.; Best, J.D. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J. Cell. Physiol., 2005, 202(3), 654-662.
[http://dx.doi.org/10.1002/jcp.20166] [PMID: 15389572]
[33]
Fu, Y.; Lee, A.S. Glucose regulated proteins in cancer progression, drug resistance and immunotherapy. Cancer Biol. Ther., 2006, 5(7), 741-744.
[http://dx.doi.org/10.4161/cbt.5.7.2970] [PMID: 16861902]
[34]
Nishimoto, A.; Kugimiya, N.; Hosoyama, T.; Enoki, T.; Li, T-S.; Hamano, K. HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells. Int. J. Oncol., 2014, 44(6), 2077-2084.
[http://dx.doi.org/10.3892/ijo.2014.2367] [PMID: 24718784]
[35]
Pi, L.; Li, X.; Song, Q.; Shen, Y.; Lu, X.; Di, B. Knockdown of glucose-regulated protein 78 abrogates chemoresistance of hypopharyngeal carcinoma cells to cisplatin induced by unfolded protein in response to severe hypoxia. Oncol. Lett., 2014, 7(3), 685-692.
[http://dx.doi.org/10.3892/ol.2013.1753] [PMID: 24527073]
[36]
Nagelkerke, A.; Bussink, J.; Sweep, F.C.; Span, P.N. The unfolded protein response as a target for cancer therapy. Biochim. Biophys. Acta (BBA)-. Rev. Can., 2014, 1846(2), 277-284.
[37]
Rosati, A.; Graziano, V.; De Laurenzi, V.; Pascale, M.; Turco, M.C. BAG3: a multifaceted protein that regulates major cell pathways. Cell Death Dis., 2011, 2(4) e141
[http://dx.doi.org/10.1038/cddis.2011.24] [PMID: 21472004]
[38]
Franceschelli, S.; Rosati, A.; Lerose, R.; De Nicola, S.; Turco, M.C.; Pascale, M. Bag3 gene expression is regulated by heat shock factor 1. J. Cell. Physiol., 2008, 215(3), 575-577.
[http://dx.doi.org/10.1002/jcp.21397] [PMID: 18286539]
[39]
Rosati, A.; Basile, A.; Falco, A.; d’Avenia, M.; Festa, M.; Graziano, V.; De Laurenzi, V.; Arra, C.; Pascale, M.; Turco, M.C. Role of BAG3 protein in leukemia cell survival and response to therapy. Biochim. Biophys. Acta, 2012, 1826(2), 365-369.
[PMID: 22710027]
[40]
Wang, H-Q.; Liu, H-M.; Zhang, H-Y.; Guan, Y.; Du, Z-X. Transcriptional upregulation of BAG3 upon proteasome inhibition. Biochem. Biophys. Res. Commun., 2008, 365(2), 381-385.
[http://dx.doi.org/10.1016/j.bbrc.2007.11.001] [PMID: 17996194]
[41]
Du, Z-X.; Meng, X.; Zhang, H-Y.; Guan, Y.; Wang, H-Q. Caspase-dependent cleavage of BAG3 in proteasome inhibitors-induced apoptosis in thyroid cancer cells. Biochem. Biophys. Res. Commun., 2008, 369(3), 894-898.
[http://dx.doi.org/10.1016/j.bbrc.2008.02.112] [PMID: 18325327]
[42]
Pasillas, M.P.; Shields, S.; Reilly, R.; Strnadel, J.; Behl, C.; Park, R.; Yates, J.R.; Klemke, R.; Gonias, S.L.; Coppinger, J.A. Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and Major Vault Protein in resistance to apoptosis in senescent cells by regulating ERK1/2 activation. Mole. Cell. Proteom., 2014, mcp(M114) 037697
[43]
Kersting, S.; Neppelenbroek, S.I.M.; Visser, H.P.J.; van Gelder, M.; Levin, M-D.; Mous, R.; Posthuma, W.; van der Straaten, H.M.; Kater, A.P. Clinical practice guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL) in the Netherlands. Clin. Lymphoma Myeloma Leuk., 2018, 18(1), 52-57.
[http://dx.doi.org/10.1016/j.clml.2017.09.015] [PMID: 29097160]
[44]
Aguirre Palma, L.M.; Flamme, H.; Gerke, I.; Kreuzer, K-A. Angiopoietins modulate survival, migration, and the components of the Ang-Tie2 pathway of Chronic Lymphocytic Leukaemia (CLL) cells in vitro. Cancer Microenviron., 2016, 9(1), 13-26.
[http://dx.doi.org/10.1007/s12307-016-0180-7] [PMID: 26846110]
[45]
Morton, L.M.; Wang, S.S.; Devesa, S.S.; Hartge, P.; Weisenburger, D.D.; Linet, M.S. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood, 2006, 107(1), 265-276.
[http://dx.doi.org/10.1182/blood-2005-06-2508] [PMID: 16150940]
[46]
DeBerardinis, R.J.; Lum, J.J.; Hatzivassiliou, G.; Thompson, C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab., 2008, 7(1), 11-20.
[http://dx.doi.org/10.1016/j.cmet.2007.10.002] [PMID: 18177721]
[47]
Kang, X.; Kong, F.; Wu, X.; Ren, Y.; Wu, S.; Wu, K.; Jiang, Z.; Zhang, W. High glucose promotes tumor invasion and increases metastasis-associated protein expression in human lung epithelial cells by upregulating heme oxygenase-1 via reactive oxygen species or the TGF-β1/PI3K/Akt signaling pathway. Cell. Physiol. Biochem., 2015, 35(3), 1008-1022.
[http://dx.doi.org/10.1159/000373928] [PMID: 25661467]
[48]
Ghosh, A.K.; Shanafelt, T.D.; Cimmino, A.; Taccioli, C.; Volinia, S.; Liu, C.G.; Calin, G.A.; Croce, C.M.; Chan, D.A.; Giaccia, A.J.; Secreto, C.; Wellik, L.E.; Lee, Y.K.; Mukhopadhyay, D.; Kay, N.E. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood, 2009, 113(22), 5568-5574.
[http://dx.doi.org/10.1182/blood-2008-10-185686] [PMID: 19336759]
[49]
Ziello, J.E.; Jovin, I.S.; Huang, Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J. Biol. Med., 2007, 80(2), 51-60.
[PMID: 18160990]
[50]
Zhou, J.; Schmid, T.; Schnitzer, S.; Brüne, B. Tumor hypoxia and cancer progression. Cancer Lett., 2006, 237(1), 10-21.
[http://dx.doi.org/10.1016/j.canlet.2005.05.028] [PMID: 16002209]
[51]
Selvendiran, K.; Bratasz, A.; Kuppusamy, M.L.; Tazi, M.F.; Rivera, B.K.; Kuppusamy, P. Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3. Int. J. Cancer, 2009, 125(9), 2198-2204.
[http://dx.doi.org/10.1002/ijc.24601] [PMID: 19623660]
[52]
Oh, M-K.; Park, H-J.; Kim, N-H.; Park, S-J.; Park, I-Y.; Kim, I-S. Hypoxia-inducible factor-1α enhances haptoglobin gene expression by improving binding of STAT3 to the promoter. J. Biol. Chem., 2011, 286(11), 8857-8865.
[http://dx.doi.org/10.1074/jbc.M110.150557] [PMID: 21224490]
[53]
Choi, J.K.; Kim, K.H.; Park, S.R.; Choi, B.H. Granulocyte macrophage colony-stimulating factor shows anti-apoptotic activity via the PI3K-NF-κB-HIF-1α-survivin pathway in mouse neural progenitor cells. Mol. Neurobiol., 2014, 49(2), 724-733.
[http://dx.doi.org/10.1007/s12035-013-8550-3] [PMID: 24022164]
[54]
Fétaud, V.; Frossard, J.L.; Farina, A.; Pastor, C.M.; Bühler, L.; Dumonceau, J.M.; Hadengue, A.; Hochstrasser, D.F.; Lescuyer, P. Proteomic profiling in an animal model of acute pancreatitis. Proteomics, 2008, 8(17), 3621-3631.
[http://dx.doi.org/10.1002/pmic.200800066] [PMID: 18686302]
[55]
Pfaffenbach, K.T.; Lee, A.S. The critical role of GRP78 in physiologic and pathologic stress. Curr. Opin. Cell Biol., 2011, 23(2), 150-156.
[http://dx.doi.org/10.1016/j.ceb.2010.09.007] [PMID: 20970977]
[56]
Ni, M.; Lee, A.S. ER chaperones in mammalian development and human diseases. FEBS Lett., 2007, 581(19), 3641-3651.
[http://dx.doi.org/10.1016/j.febslet.2007.04.045] [PMID: 17481612]
[57]
Hayashi, T.; Saito, A.; Okuno, S.; Ferrand-Drake, M.; Chan, P.H. Induction of GRP78 by ischemic preconditioning reduces endoplasmic reticulum stress and prevents delayed neuronal cell death. J. Cereb. Blood Flow Metab., 2003, 23(8), 949-961.
[http://dx.doi.org/10.1097/01.WCB.0000077641.41248.EA] [PMID: 12902839]
[58]
Rao, R.V.; Peel, A.; Logvinova, A.; del Rio, G.; Hermel, E.; Yokota, T.; Goldsmith, P.C.; Ellerby, L.M.; Ellerby, H.M.; Bredesen, D.E. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett., 2002, 514(2-3), 122-128.
[http://dx.doi.org/10.1016/S0014-5793(02)02289-5] [PMID: 11943137]
[59]
Brewer, J.W. Regulatory crosstalk within the mammalian unfolded protein response. Cell. Mol. Life Sci., 2014, 71(6), 1067-1079.
[http://dx.doi.org/10.1007/s00018-013-1490-2] [PMID: 24135849]
[60]
Liu, Y.; Steiniger, S.C.; Kim, Y.; Kaufmann, G.F.; Felding-Habermann, B.; Janda, K.D. Mechanistic studies of a peptidic GRP78 ligand for cancer cell-specific drug delivery. Mol. Pharm., 2007, 4(3), 435-447.
[http://dx.doi.org/10.1021/mp060122j] [PMID: 17373820]
[61]
Lizardo, M.M.; Morrow, J.J.; Miller, T.E.; Hong, E.S.; Ren, L.; Mendoza, A.; Halsey, C.H.; Scacheri, P.C.; Helman, L.J.; Khanna, C. Upregulation of glucose-regulated protein 78 in metastatic cancer cells is necessary for lung metastasis progression. Neoplasia, 2016, 18(11), 699-710.
[http://dx.doi.org/10.1016/j.neo.2016.09.001] [PMID: 27973325]
[62]
Wang, X-Q.; Aka, J.A.; Li, T.; Xu, D.; Doillon, C.J.; Lin, S-X. Inhibition of 17beta-hydroxysteroid dehydrogenase type 7 modulates breast cancer protein profile and enhances apoptosis by down-regulating GRP78. J. Steroid Biochem. Mol. Biol., 2017, 172, 188-197.
[http://dx.doi.org/10.1016/j.jsbmb.2017.06.009] [PMID: 28645527]
[63]
Wang, M.; Ye, R.; Barron, E.; Baumeister, P.; Mao, C.; Luo, S.; Fu, Y.; Luo, B.; Dubeau, L.; Hinton, D.R.; Lee, A.S. Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis. Cell Death Differ., 2010, 17(3), 488-498.
[http://dx.doi.org/10.1038/cdd.2009.144] [PMID: 19816510]
[64]
Li, J.; Lee, A.S. Stress induction of GRP78/BiP and its role in cancer. Curr. Mol. Med., 2006, 6(1), 45-54.
[http://dx.doi.org/10.2174/156652406775574523] [PMID: 16472112]
[65]
Kania, E.; Pająk, B.; Orzechowski, A. Calcium homeostasis and ER stress in control of autophagy in cancer cells. BioMed Res. Int., 2015, 2015 Article ID 352794
[http://dx.doi.org/10.1155/2015/352794]
[66]
Casas, C. GRP78 at the centre of the stage in cancer and neuroprotection. Front. Neurosci., 2017, 11, 177.
[http://dx.doi.org/10.3389/fnins.2017.00177] [PMID: 28424579]
[67]
Liu, Y.; Yang, L.; Chen, K-L.; Zhou, B.; Yan, H.; Zhou, Z-G.; Li, Y. Knockdown of GRP78 promotes apoptosis in pancreatic acinar cells and attenuates the severity of cerulein and LPS induced pancreatic inflammation. PLoS One, 2014, 9(3) e92389
[http://dx.doi.org/10.1371/journal.pone.0092389] [PMID: 24643222]
[68]
Liu, R.; Li, X.; Gao, W.; Zhou, Y.; Wey, S.; Mitra, S.K.; Krasnoperov, V.; Dong, D.; Liu, S.; Li, D.; Zhu, G.; Louie, S.; Conti, P.S.; Li, Z.; Lee, A.S.; Gill, P.S. Monoclonal antibody against cell surface GRP78 as a novel agent in suppressing PI3K/AKT signaling, tumor growth, and metastasis. Clin. Cancer Res., 2013, 19(24), 6802-6811.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1106] [PMID: 24048331]
[69]
Huergo-Zapico, L.; Gonzalez-Rodriguez, A.P.; Contesti, J.; Gonzalez, E.; López-Soto, A.; Fernandez-Guizan, A.; Acebes-Huerta, A.; de Los Toyos, J.R.; Lopez-Larrea, C.; Groh, V.; Spies, T.; Gonzalez, S. Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding. Cancer Immunol. Immunother., 2012, 61(8), 1201-1210.
[http://dx.doi.org/10.1007/s00262-011-1195-z] [PMID: 22215138]
[70]
Lee, J.H.; Yoon, Y.M.; Lee, S.H. Hypoxic preconditioning promotes the bioactivities of mesenchymal stem cells via the HIF-1α-GRP78-Akt axis. Int. J. Mol. Sci., 2017, 18(6), 1320.
[http://dx.doi.org/10.3390/ijms18061320]
[71]
Shi, H.; Chen, W.; Dong, Y.; Lu, X.; Zhang, W.; Wang, L. BAG3 promotes chondrosarcoma progression by upregulating the expression of β-catenin. Mol. Med. Rep., 2018, 17(4), 5754-5763.
[http://dx.doi.org/10.3892/mmr.2018.8611] [PMID: 29484408]
[72]
Chen, H-Y.; Liu, P.; Sun, M.; Wu, L-Y.; Zhu, H-Y.; Qiao, C.; Dong, H-J.; Zhu, D-X.; Xu, W.; Li, J-Y. [Bag3 gene expression in chronic lymphocytic leukemia and its association with patients’ prognosis]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2010, 18(4), 838-842.
[PMID: 20723284]
[73]
Rosati, A.; Bersani, S.; Tavano, F.; Dalla Pozza, E.; De Marco, M.; Palmieri, M.; De Laurenzi, V.; Franco, R.; Scognamiglio, G.; Palaia, R.; Fontana, A.; di Sebastiano, P.; Donadelli, M.; Dando, I.; Medema, J.P.; Dijk, F.; Welling, L.; di Mola, F.F.; Pezzilli, R.; Turco, M.C.; Scarpa, A. Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival. Am. J. Pathol., 2012, 181(5), 1524-1529.
[http://dx.doi.org/10.1016/j.ajpath.2012.07.016] [PMID: 22944597]
[74]
Kong, D-H.; Zhang, Q.; Meng, X.; Zong, Z-H.; Li, C.; Liu, B-Q.; Guan, Y.; Wang, H-Q. BAG3 sensitizes cancer cells exposed to DNA damaging agents via direct interaction with GRP78. Biochim. Biophys. Acta, 2013, 1833(12), 3245-3253.
[http://dx.doi.org/10.1016/j.bbamcr.2013.09.013] [PMID: 24080088]
[75]
d’Avenia, M.; Guerriero, L.; Rosati, A.; Turco, M.C. BAG3 (Bcl-2 associated athanogene 3). Atlas Genet. Cytogenet. Oncol. Hematol., 2014, 18(10), 704-708.
[76]
Zhu, H.; Liu, P.; Li, J. 4.5 Expression of the BAG3 gene in chronic lymphocytic leukemia and its clinical significance. Clin. Lymphoma Myeloma Leuk., 2011, 11, S220.
[http://dx.doi.org/10.1016/j.clml.2011.09.125]


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VOLUME: 20
ISSUE: 4
Year: 2020
Page: [429 - 436]
Pages: 8
DOI: 10.2174/1871520619666191211101357
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